Association analysis of myosin IXB and type 1 diabetes

Persengiev, Stephan P.; Koeleman, Bobby P. C.; Downes, Kate; Valdigem, Gustavo; Slik, Arno R. van der; Eerligh, Peter; Monsuur, Alienke J.; Bruining, G. J.; Wijmenga, Cisca; Todd, John A.; Roep, Bart O.; Alizadeh, Behrooz Z.

doi:10.1016/j.humimm.2010.03.002

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…Future work will have to determine the precise pathways and factors that control localized Myo9b activity in DCs. Based on our findings and the notion that Myo9b may play a role in inflammatory bowel disease and other autoimmune diseases (19,20), it will be of interest to determine to which extent the loss of Myo9b affects peripheral tolerance under homeostatic conditions and immune responses toward infections and allergic reactions that are mediated by DCs.…”

Section: Discussionmentioning

confidence: 94%

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Dendritic Cell Motility and T Cell Activation Requires Regulation of Rho-Cofilin Signaling by the Rho-GTPase Activating Protein Myosin IXb

Xu¹,

Pektor

Balkow

et al. 2014

The Journal of Immunology

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Directed migration of stimulated dendritic cells (DCs) to secondary lymphoid organs and their interaction with Ag-specific T cells is a prerequisite for the induction of primary immune responses. In this article, we show that murine DCs that lack myosin IXB (Myo9b), a motorized negative regulator of RhoA signaling, exhibit increased Rho signaling activity and downstream acto-myosin contractility, and inactivation of the Rho target protein cofilin, an actin-depolymerizing factor. On a functional level, Myo9b−/− DCs showed impaired directed migratory activity both in vitro and in vivo. Moreover, despite unaltered Ag presentation and costimulatory capabilities, Myo9b−/− DCs were poor T cell stimulators in vitro in a three-dimensional collagen matrix and in vivo, associated with altered DC–T cell contact dynamics and T cell polarization. Accordingly, Myo9b−/− mice showed an attenuated ear-swelling response in a model of contact hypersensitivity. The impaired migratory and T cell stimulatory capacity of Myo9b−/− DCs was restored in large part by pharmacological activation of cofilin. Taken together, these results identify Myo9b as a negative key regulator of the Rho/RhoA effector Rho-kinase [Rho-associated coiled-coil–forming kinase (ROCK)]/LIM domain kinase signaling pathway in DCs, which controls cofilin inactivation and myosin II activation and, therefore may control, in part, the induction of adaptive immune responses.

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Section: Discussionmentioning

confidence: 94%

“…Myo9b is abundantly expressed in various cell types of the immune system (13,18) and appears to contribute to the development of autoimmune diseases (19,20). Thus, we explored the relevance of Myo9b for DC functions using Myo9b-deficient mice.…”

mentioning

confidence: 99%

Dendritic Cell Motility and T Cell Activation Requires Regulation of Rho-Cofilin Signaling by the Rho-GTPase Activating Protein Myosin IXb

Xu¹,

Pektor

Balkow

et al. 2014

The Journal of Immunology

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show abstract

“…DNA concentration was determined with the quantification NAN-ODROP equipment (Thermo Fisher Scientific, USA). Determination of rs2305767 C/T, rs1457092 A/C and rs2305764 A/G (11,(18)(19)(20)(21) in MYO9B was performed using Taqman probes.…”

Section: Genetic Studiesmentioning

confidence: 99%

Frequency of MYO9B polymorphisms in celiac patients and controls

Loeff

Araya

Pérez-Bravo

2012

Rev. esp. enferm. dig.

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“…MYO9B is one of the most interesting candidate genes and is reported to be associated with celiac disease [10], DM type 1 [11,12], and IBD [13][14][15][16]. MYO9B at chromosome 19 encodes a single motor protein [17], which is involved in remodeling of the cytoskeleton and influences TJ assembly [18,19].…”

Section: Introductionmentioning

confidence: 99%

“…These 3 genes (MAGI2, PARD3, and MYO9B) were associated with autoimmune diseases in independent European studies [10,[12][13][14][15][16]24,27], and we undertook a replication study in a Canadian IBD cohort.…”

Section: Introductionmentioning

confidence: 99%